Male factor infertility and placental pathology in singleton live births conceived with in vitro fertilization.

PURPOSE: We sought to determine whether pregnancies conceived in those with male factor infertility have unique placental pathology profiles compared to those undergoing infertility treatments for other indications. METHODS: This was a retrospective cohort study of placental pathology from 464 live births conceived from autologous fresh IVF cycles at an academic fertility center from 2004 to 2017. Placental pathology was compared between live births arising from patients with male factor infertility alone and those with another infertility diagnosis. Placental outcomes were compared with parametric or non-parametric tests; logistic regression was performed to account for potential confounders. RESULTS: Compared to cycles performed for a non-male factor diagnosis, male factor infertility cycles had a higher mean paternal age (38.2 years vs. 36.5 years, p < 0.001), a higher female mean BMI (24.3 vs. 23.3 kg/m2, p = 0.01), and a lower day 3 follicle stimulating hormone (FSH) level (6.8 vs. 7.3 IU/mL, p = 0.02). The mean numbers of embryos transferred, and day of transfer were similar between groups, and more cycles used ICSI in the male factor infertility group (90.6% vs. 22.5%, p < 0.001). Placental pathology in our adjusted model was similar between the male factor and non-male factor groups. In our unadjusted subgroup analysis, cycles for male factor using ICSI appeared to lead to more small placentas by weight compared to cycles performed with conventional insemination (45.8% < 10th percentile vs. 18.8%, p = 0.04). CONCLUSION: Male factor infertility is not associated with significantly different placental pathology compared to other infertility diagnoses.

Narrow pH tolerance found for a microbial fuel cell treating winery wastewater.

AIMS: The use of microbial fuel cells (MFC) to treat winery wastewater is promising; however, an initial acidic pH, fluctuating chemical oxygen demand (COD) levels and a lack of natural buffering in these wastewaters make providing a suitable buffer system at an ideal buffer to COD ratio. METHODS AND RESULTS: A lab scale MFC was designed, inoculated with anaerobic winery sludge and fed with synthetic winery wastewater. It was observed that at pH 6·5, the MFC performed best, the maximum output voltage was 0·63 ± 0·01 V for 60 ± 3 h, and the COD removal efficiency reached 77 ± 7%. The electrogens were affected by pH much more than the bulk COD degrading organisms. Fluorescent in situ hybridization suggested Betaproteobacteria played a significant role in electron transfer. CONCLUSIONS: A ratio of 1 mmol l-1 phosphate buffer to 100 mg l-1 COD was ideal to maintain a stable pH for MFCs treating synthetic winery wastewater. SIGNIFICANCE AND IMPACT OF THE STUDY: The results find the narrow pH tolerance for MFCs treating winery wastewater and demonstrate the significance of pH and buffer to COD ratio for steady performance of MFCs.

Case epidemiology from the first three years of a pilot laboratory-based surveillance system for elevated blood-lead concentrations among children in England, 2014-17: implications for public health action.

BACKGROUND: Children incur lead toxicity even at low blood-lead concentrations (BLCs), and testing in England is opportunistic. We described epidemiology of cases notified to a passive laboratory-based surveillance system (SS), the Lead Poisoning in Children (LPIC) SS to inform opportunities to prevent lead exposure in children in England. METHODS: Surveillance population: children <16 years of age and resident in England during the reporting period September 2014-17. Case definition: children with BLC ≥0.48 µmol/l (10 µg/dl). We extracted case demographic/location data and linked it with laboratory, area-level population and socio-economic status (SES) data. We described case BLCs and calculated age-, gender- and SES-specific notification rates, and age-sex standardised regional notification rates. RESULTS: Between 2014 and 2017 there were 86 newly notified cases, giving an annual average notification rate of 2.76 per million children aged 0-15 years. Regionally, rates varied from 0.36 to 9.89 per million. Rates were highest in the most deprived quintile (5.38 per million), males (3.75 per million) and children aged 1-4 years (5.89 per million). CONCLUSIONS: Males, children aged 1-4 years, and children in deprived areas may be at higher risk, and could be targeted for primary prevention. Varied regional notification rates suggest differences in clinician awareness of lead exposure and risk factors; guidelines standardising the indications for BLC-testing may assist secondary prevention.

The Clock Counts - Length Effects in English Dyslexic Readers.

In reading, length effects (LEs) are defined as an increment in the time taken to read as a function of word length and may indicate whether reading is proceeding in an efficient whole word fashion or by serial letter processing. LEs are generally considered to be a pathognomonic symptom of developmental dyslexia (DD) and predominantly have been investigated in transparent orthographies where reading impairment is characterized as slow and effortful. In the present study a sample of 18 adult participants with DD were compared to a matched sample of typical developing readers to investigate whether the LE is a critical aspect of DD in an opaque orthography, English. We expected that the DD group would present with marked LEs, in both words and non-words, compared to typical developing readers. The presence of LEs in the DD group confirmed our prediction. These effects were particularly strong in low frequency words and in non-words, as observed in reading speed. These preliminary findings may have important theoretical implications for current understanding of DD.

Revisiting the sternocleidomastoid flap as a reconstructive option in head and neck surgery.

BACKGROUND: The sternocleidomastoid can be used as a pedicled flap in head and neck reconstruction. It has previously been associated with high complication rates, likely due in part to the variable nature of its blood supply. OBJECTIVE: To provide clinicians with an up-to-date review of clinical outcomes of sternocleidomastoid flap surgery in head and neck reconstruction, integrated with a review of vascular anatomical studies of the sternocleidomastoid. METHODS: A literature search of the Medline and Web of Science databases was conducted. Complications were analysed for each study. The trend in success rates was analysed by date of the study. RESULTS: Reported complication rates have improved over time. The preservation of two vascular pedicles rather than one may have contributed to improved outcomes. CONCLUSION: The sternocleidomastoid flap is a versatile option for patients where prolonged free flap surgery is inappropriate. Modern vascular imaging techniques could optimise pre-operative planning.

Six-month outcomes after restrictive or liberal transfusion for cardiac surgery (TRICS III trial).

CLINICAL QUESTION: Is transfusing red cell components using a restrictive transfusion threshold (Hb < 75 g L-1 ) as safe as a liberal transfusion threshold (Hb < 95 g L-1 in intensive care and < 85 g L-1 outside intensive care) during and after cardiac surgery for adults at moderate to high risk of death? EVIDENCE FROM TRIAL: In adults undergoing cardiac surgery who were at moderate to high risk for death, using a restrictive red-cell transfusion threshold was as safe as a liberal red cell transfusion threshold (composite outcome of death from any cause, myocardial infarction, stroke or new-onset renal failure with dialysis at 6 months after surgery).

Cost-effectiveness of alternative changes to a national blood collection service.

OBJECTIVES: To evaluate the cost-effectiveness of changing opening times, introducing a donor health report and reducing the minimum inter-donation interval for donors attending static centres. BACKGROUND: Evidence is required about the effect of changes to the blood collection service on costs and the frequency of donation. METHODS/MATERIALS: This study estimated the effect of changes to the blood collection service in England on the annual number of whole-blood donations by current donors. We used donors' responses to a stated preference survey, donor registry data on donation frequency and deferral rates from the INTERVAL trial. Costs measured were those anticipated to differ between strategies. We reported the cost per additional unit of blood collected for each strategy versus current practice. Strategies with a cost per additional unit of whole blood less than £30 (an estimate of the current cost of collection) were judged likely to be cost-effective. RESULTS: In static donor centres, extending opening times to evenings and weekends provided an additional unit of whole blood at a cost of £23 and £29, respectively. Introducing a health report cost £130 per additional unit of blood collected. Although the strategy of reducing the minimum inter-donation interval had the lowest cost per additional unit of blood collected (£10), this increased the rate of deferrals due to low haemoglobin (Hb). CONCLUSION: The introduction of a donor health report is unlikely to provide a sufficient increase in donation frequency to justify the additional costs. A more cost-effective change is to extend opening hours for blood collection at static centres.

NOX1 loss-of-function genetic variants in patients with inflammatory bowel disease.

Genetic defects that affect intestinal epithelial barrier function can present with very early-onset inflammatory bowel disease (VEOIBD). Using whole-genome sequencing, a novel hemizygous defect in NOX1 encoding NAPDH oxidase 1 was identified in a patient with ulcerative colitis-like VEOIBD. Exome screening of 1,878 pediatric patients identified further seven male inflammatory bowel disease (IBD) patients with rare NOX1 mutations. Loss-of-function was validated in p.N122H and p.T497A, and to a lesser degree in p.Y470H, p.R287Q, p.I67M, p.Q293R as well as the previously described p.P330S, and the common NOX1 SNP p.D360N (rs34688635) variant. The missense mutation p.N122H abrogated reactive oxygen species (ROS) production in cell lines, ex vivo colonic explants, and patient-derived colonic organoid cultures. Within colonic crypts, NOX1 constitutively generates a high level of ROS in the crypt lumen. Analysis of 9,513 controls and 11,140 IBD patients of non-Jewish European ancestry did not reveal an association between p.D360N and IBD. Our data suggest that loss-of-function variants in NOX1 do not cause a Mendelian disorder of high penetrance but are a context-specific modifier. Our results implicate that variants in NOX1 change brush border ROS within colonic crypts at the interface between the epithelium and luminal microbes.

Intra-Abdominal Hypertension and Abdominal Compartment Syndrome after Abdominal Wall Reconstruction: Quaternary Syndromes?

BACKGROUND AND AIMS: Reconstruction with reconstitution of the container function of the abdominal compartment is increasingly being performed in patients with massive ventral hernia previously deemed inoperable. This situation places patients at great risk of severe intra-abdominal hypertension and abdominal compartment syndrome if organ failure ensues. Intra-abdominal hypertension and especially abdominal compartment syndrome may be devastating systemic complications with systematic and progressive organ failure and death. We thus reviewed the pathophysiology and reported clinical experiences with abnormalities of intra-abdominal pressure in the context of abdominal wall reconstruction. MATERIAL AND METHODS: Bibliographic databases (1950-2015), websites, textbooks, and the bibliographies of previously recovered articles for reports or data relating to intra-abdominal pressure, intra-abdominal hypertension, and the abdominal compartment syndrome in relation to ventral, incisional, or abdominal hernia repair or abdominal wall reconstruction. RESULTS: Surgeons should thus consider and carefully measure intra-abdominal pressure and its resultant effects on respiratory parameters and function during abdominal wall reconstruction. The intra-abdominal pressure post-operatively will be a result of the new intra-peritoneal volume and the abdominal wall compliance. Strategies surgeons may utilize to ameliorate intra-abdominal pressure rise after abdominal wall reconstruction including temporizing paralysis of the musculature either temporarily or semi-permanently, pre-operative progressive pneumoperitoneum, permanently removing visceral contents, or surgically releasing the musculature to increase the abdominal container volume. In patients without complicating shock and inflammation, and in whom the abdominal wall anatomy has been so functionally adapted to maximize compliance, intra-abdominal hypertension may be transient and tolerable. CONCLUSIONS: Intra-abdominal hypertension/abdominal compartment syndrome in the specific setting of abdominal wall reconstruction without other complication may be considered as a quaternary situation considering the classification nomenclature of the Abdominal Compartment Society. Greater awareness of intra-abdominal pressure in abdominal wall reconstruction is required and ongoing study of these concerns is required.

Randomised controlled trial comparing marksmanship following application of a tourniquet or haemostatic clamp in healthy volunteers.

BACKGROUND: In a care under fire situation, a first line response to haemorrhage is to apply a tourniquet and return fire. However, there is little understanding of how tourniquets and other haemorrhage control devices impact marksmanship. METHODS: We compared the impact of the iTClamp and the Combat Application Tourniquet (CAT) on marksmanship. Following randomisation (iTClamp or CAT), trained marksmen fired an AR15 at a scaled silhouette target in prone unsupported position (shooting task). Subjects then attempted to complete the shooting task at 5, 10, 15, 30 and 60 min post-haemorrhage control device application. RESULTS: All of the clamp groups (n=7) completed the 60 min shooting task. Five CAT groups (n=6) completed the 5 min shooting task and one completed the 5 and 10 min shooting task before withdrawing. Four CAT groups were stopped due to unsafe handling; two stopped due to pain. When examining hits on mass (HOM) for the entire shooting task, there was no significant difference between tourniquet and iTClamp HOM at 5 min (p=0.18). However, there was a significant difference at 10 min, p=0.003 with tourniquet having significantly fewer HOM (1.7±2.7 HOM) than the iTClamp (8.1±3.3 HOM) group. The total effective HOM for the entire 60 min shooting task showed that the iTClamp group achieved significantly (p=0.001) more HOM than the tourniquet group. Over the entire 60 min shooting exercise, the iTClamp group achieved a median 72% (52/72) of available HOM while the tourniquet group obtained 19% (14/72). CONCLUSIONS: Application of a tourniquet to the dominant arm negates effective return of fire in a care under fire setting after a brief time window. Haemorrhage control devices that preserve function may have a role in care under fire situations, as preserving effectiveness in returning fire has obvious operational merits.

Novel statistical approach for evaluating flow cytometric in vitro micronucleus data.

Statistical methods currently recommended for analysis of in vitro micronucleus data are based on small sample sizes. The tests are designed to evaluate linear trends and differences between treated and control samples. When using flow cytometric analysis, >5 times the number of cells are easily evaluated, and the variance estimates from these large samples are small. Application of these recommended tests to large samples resulted in statistically significant outcomes which were not considered to be biologically meaningful. Alternative statistical methods for testing trends and differences among treatments that were either widely used, or sample-size independent, were investigated. Using data from 95 experiments (from 2011-2013) where 19% of the experiments were considered positive, results for the various statistical methods were compared. When using either the recommended or alternate methods, 42-68% of the experiments resulted in statistically significant results (p < 0.05). A new concept was then tested using the same data sets: the "z' factor", designed to identify 'hits' during high throughput screening. Using this simple-to-compute statistic the number of significant calls was reduced to 27%. Then, when combined with a biological criterion based on historical vehicle control data, there was restoration of the original positive frequency (19%). Given the larger sample sizes evaluated using flow cytometry, we have demonstrated that traditional statistical tests may be overly sensitive to small changes in micronucleus induction, and that a simple-to-compute index of separation (z') may be a better tool for analysis, provided that the response is first determined to be biologically meaningful. Environ. Mol. Mutagen. 57:589-604, 2016. © 2016 Wiley Periodicals, Inc.

Interventions to reduce vasovagal reactions in blood donors: a systematic review and meta-analysis.

Vasovagal reactions (VVRs) in blood donors have significant implications for the welfare of donors, donor retention and the management of donor sessions. We present a systematic review of interventions designed to prevent or reduce VVRs in blood donors. Electronic databases were searched for eligible randomised trials to March 2015. Data on study design and outcomes were extracted and pooled using random effects meta-analyses. Sixteen trials met the inclusion criteria: five trials (12 042 participants) of pre-donation water, eight trials (3500 participants) of applied muscle tension (AMT) and one trial each of AMT combined with water, caffeine, audio-visual distraction and/or social support. In donors receiving pre-donation water, the relative risk (RR) compared with controls for VVRs was 0·79 [95% confidence interval (CI) 0·70-0·89, P < 0·0001] and the mean difference (MD) in severity of VVRs measured with the Blood Donation Reactions Inventory (BDRI) score was -0·32 (95% CI -0·51 to -0·12, P < 0·0001). Excluding trials with a high risk of selection bias, the RR for VVRs was 0·70 (95% CI 0·45-1·11, P = 0·13). In donors who received AMT, there was no difference in the risk of chair recline in response to donor distress from controls (RR 0·76, 95% CI 0·53-1·10, P = 0·15), although the MD in BDRI score was -0·07 (95% CI -0·11 to -0·03, P = 0·0005). There was insufficient data to perform meta-analysis for other interventions. Current evidence on interventions to prevent or reduce VVRs in blood donors is indeed limited and does not provide strong support for the administration of pre-donation water or AMT during donation. Further large trials are required to reliably evaluate the effect of these and other interventions in the prevention of VVRs.

A venue-based analysis of the reach of a targeted outreach service to deliver opportunistic community NHS Health Checks to 'hard-to-reach' groups.

OBJECTIVES: Opportunistic outreach services have been commissioned to overcome potential barriers to uptake, by offering health checks in accessible community venues. This study aimed to evaluate the ability of an outreach health check service to reach key target groups: men, people of South Asian ethnicity and people from deprived areas. The comparator was the health check service provided by GP practices. One aim was to investigate whether the addition of an outreach service would result in a higher percentage of health checks being done for people from the target groups compared to a GP-based service alone. The second aim was to assess which types of venues used for outreach health checks were most effective in reaching these groups. STUDY DESIGN: Evaluation of Public Health Programme with retrospective control group comparison. METHODS: The percentages of completed health checks in men, people of South Asian ethnicity, and participants registered at general practices with lowest quintile area-level deprivation status were compared between all opportunistic community checks conducted by the Outreach Service over a ten month period and checks conducted in general practice in a partially-overlapping time period of the same financial year. For the venue-based comparison of Outreach Service checks, the number of checks per visit and percentage of checks in each target group were calculated for each venue. RESULTS: Of 3849 Outreach Service checks, 38% were in men (compared to 50% of checks conducted in Primary Care), and 11% were in people of South Asian ethnicity (compared to 3% in Primary Care). 3558 Outreach check participants were registered with a general practice in the County (92%), and of these, 32% of checks were in people registered with a general practice in the lowest deprivation quintile (compared to 13% of checks in Primary Care). There were 519 visits by the outreach service to 23 different types of venue. Certain venues recorded large numbers of checks e.g. supermarkets and libraries, but they were not always the most efficient places to recruit people for checks. Mosques and bus stations were the venues with the broadest reach to all target groups. Other venues, despite having lower turnover or recruitment rates, were still good settings to reach specific target groups. CONCLUSION: The NHS Health Check can successfully be targeted at people from deprived areas and people of South Asian ethnicity using a targeted opportunistic community outreach approach. Our findings show that the reach to different groups varies substantially by venue, and therefore best results may be achieved by combining venues and strategies specific to the target group.

High proportions of regulatory T cells in PBSC grafts predict improved survival after allogeneic haematopoietic SCT.

Regulatory T cells (Tregs) modulate immune responses and improve survival in murine transplant models. However, whether the Treg content of allogeneic cell grafts influences the outcome in human haematopoietic stem cell (HSC) transplantation is not well established. In a prospective study of 94 adult allogeneic PBSC transplants (60% unrelated; 85% reduced intensity conditioning), the median Treg (CD3(+)CD4(+)CD25(+)FOXP3(+)CD127(dim/-)) dose transplanted was 4.7 × 10(6)/kg, with Tregs accounting for a median of 2.96% of CD4(+) T cells. Patients transplanted with grafts containing a Treg/CD4(+) T-cell ratio above the median had a 3-year overall survival of 75%, compared with 49% in those receiving grafts with a Treg/CD4(+) T-cell ratio below the median (P=0.02), with a 3-year non-relapse mortality of 13% and 35%, respectively (P=0.02). In multivariate analysis, a high graft Treg/CD4(+) T-cell ratio was an independent predictor of lower non-relapse mortality (hazard ratio (HR), 0.30; P=0.02), improved overall survival (HR, 0.45; P=0.03) and improved sustained neutrophil (HR, 0.52; P=0.002), platelet (HR, 0.51; P<0.001) and lymphocyte (HR, 0.54; P=0.009) recovery. These data support the hypothesis that the proportion of Tregs in allogeneic HSC grafts influences clinical outcome and suggest that Treg therapies could improve allogeneic HSC transplantation.